High blood pressure (BP) is present in up to 78% of older adults in the United States, is more prevalent in African Americans than other ethnic groups, and is a leading cause of cardiovascular disease mortality. Social- environmental stress and social support factors, such as individual socioeconomic status (SES), have been linked to high BP, as have related physiological mechanisms such as hypothalamic-pituitary-adrenal (HPA) secretion of glucocorticoid stress hormones (e.g. cortisol), and genetic factors such as polymorphisms in glucocorticoid receptor (GR) genes. However, few studies have integrated these factors in African Americans, and social-environmental factors have often been measured at the individual- but not at the community-level, giving little insight into community factors (e.g. community SES) relevant to population-level efforts to understand BP regulatory mechanisms and health disparities. Investigating how these factors interact to influence BP outcomes may afford a better understanding of BP etiology and contribute to successful prevention efforts. Additionally, ecological, psychosocial, and biological theories of health may guide such an integrated investigation. Thus, the aim of the proposed study is to examine how community-level social- environmental factors interact with GR polymorphisms to predict cortisol and high BP, and whether cortisol mediates the association of social-environmental factors with BP as an underlying physiologic mechanism, as has been well established in clinical and experimental models. Data for each variable will be collected within an existing sample of older adult African Americans (N=434;Mage=51.2 years) nested within three communities as part of the on-going NIH-funded PATH trial. The PI of the trial, Dr. Dawn Wilson, is the primary sponsor of this application. Participants will attend health screenings during which data for target variables will be collected. Social-environmental variables will include census-derived community-level SES, community crime rates, and community connectedness measured via questionnaire. Saliva samples will allow measurement of morning and afternoon cortisol as a marker of basal HPA functioning and stress. Genomic DNA for three single nucleotide polymorphisms (SNPs) previously linked to social-environmental and physiologic mechanisms of high BP (Bcl1, rs 41423247;FKBP5, rs1360780;92, rs6198) will be extracted from buccal swab samples and assayed via polymerase chain reaction, under the guidance of Dr. Matthew Kostek, a co-sponsor of this application. Structural equation modeling and regression will be applied to test stated study aims and hypotheses, with relevant covariates such as BP medication status, age, and sex included in statistical models. Potential clustering by community will be controlled by examining intra-class correlation coefficients. Thus, through the integrated study of social-environmental, physiologic, and genetic factors, this investigation will contribute to a comprehensive conceptualization of high BP and disparity in underserved African American populations, and has the potential to inform innovative prevention approaches and public policy. PUBLIC HEALTH RELEVANCE: The proposed study will expand our understanding of social-environmental, physiologic, and genetic effects on high blood pressure (BP) in African Americans. This project will ultimately inform prevention programs in reducing high BP, chronic disease, and health disparities experienced by African Americans.